dbSNP rs764405239: PIN4:p.Met3Val (chrX-72181717-A-G) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The ENST00000664196.1(PIN4):c.7A>G(p.Met3Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000712 in 982,699 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M3L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 24)

Exomes 𝑓: 0.0000071 ( 0 hom. 4 hem. )

Consequence

PIN4
ENST00000664196.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.20

Publications

0 publications found

Variant links:

Genes affected

PIN4 (HGNC:8992): (peptidylprolyl cis/trans isomerase, NIMA-interacting 4) This gene encodes a member of the parvulin subfamily of the peptidyl-prolyl cis/trans isomerase protein family. The encoded protein catalyzes the isomerization of peptidylprolyl bonds, and may play a role in the cell cycle, chromatin remodeling, and/or ribosome biogenesis. The encoded protein may play an additional role in the mitochondria. [provided by RefSeq, Dec 2009]

PIN4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.04496005).

BS2

High Hemizygotes in GnomAdExome4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIN4	NM_001170747.1 link	c.7A>G	p.Met3Val	missense_variant	Exon 1 of 4		NP_001164218.1	Q9Y237-3
PIN4	NM_006223.4 link	c.-69A>G		upstream_gene_variant		ENST00000373669.8	NP_006214.3	Q9Y237-1
PIN4	NR_033187.2 link	n.-40A>G		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIN4	ENST00000373669.8 link	c.-69A>G		upstream_gene_variant		1	NM_006223.4	ENSP00000362773.3		Q9Y237-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000219

AC:

AN:

182767

AF XY:

0.0000446

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000712

AC:

AN:

982699

Hom.:

Cov.:

AF XY:

0.0000137

AC XY:

AN XY:

291311

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25021

American (AMR)

AF:

0.00

AC:

AN:

35077

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18667

East Asian (EAS)

AF:

0.00

AC:

AN:

29962

South Asian (SAS)

AF:

0.000115

AC:

AN:

52163

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40481

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2732

European-Non Finnish (NFE)

AF:

0.00000136

AC:

AN:

736194

Other (OTH)

AF:

0.00

AC:

AN:

42402

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000247

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.026

(source)

DANN

Benign

0.60

DEOGEN2

Benign

0.043

T;.;.

FATHMM_MKL

Benign

0.020

LIST_S2

Benign

0.30

.;T;T

M_CAP

Benign

0.0021

MetaRNN

Benign

0.045

T;T;T

MetaSVM

Benign

-0.96

PhyloP100

-1.2

PrimateAI

Benign

0.31

PROVEAN

Benign

0.070

N;N;N

REVEL

Benign

0.045

Sift

Pathogenic

0.0

D;D;D

Sift4G

Benign

0.49

T;T;T

Polyphen

0.0

.;.;B

Vest4

0.014

MutPred

0.22

Loss of ubiquitination at K8 (P = 0.0877);Loss of ubiquitination at K8 (P = 0.0877);Loss of ubiquitination at K8 (P = 0.0877);

MVP

0.093

MPC

0.11

ClinPred

0.049

GERP RS

-8.3

PromoterAI

-0.13

Neutral

(source)

gMVP

0.28

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

rs764405239

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over